This proposal is designed to evaluate the effect of aging on three pathways of drug metabolism in man. They are: microsomal oxidation and O-glucuronidation, and N-acetylation. Model compounds (amobarbital, oxazepam, and isoniazid) primarily eliminated by each of these pathways will be given to healthy subjects in 3 age ranges, and concentrations in blood will be measured. Intrinsic clearance, which provides an estimate of the overall activity of each pathway independent of blood flow and plasma protein binding, will be calculated for each drug in each subject. This will allow comparisons of activity of each of these three pathways to be made between the age ranges studied, to determine if changes in activity do occur, and, if so, whether they occur in parallel for all pathways. The proposed research takes advantage of recent concepts relating blood flow, binding, and hepatocellular activity to hepatic clearance. The data generated will provide quantitative information about the magnitude and relevance of changes in drug metabolism in the elderly patient population.